A systematic review and meta-analysis of the association between uric acid levels and chronic kidney disease

The function of uric acid (UA) in the genesis and evolution of chronic kidney disease (CKD) has motivated numerous studies, but the results remain inconclusive. We sought to conduct a systematic review and meta-analysis of cohort studies aiming to analyze the association of UA levels with the incidence and progression of CKD. Pubmed/Medline, Lilacs/Bireme and Web of Science were searched to identify eligible studies, following the PRISMA protocol. Data were presented for CKD incidence and progression separately. For the meta-analysis, studies with data stratified by subgroups according to serum UA levels were selected. The inverse variance-weighted random effects model was used to generate a combined effect estimate. Meta-regressions were performed to identify the causes of heterogeneity. The Newcastle–Ottawa Scale was used to assess the risk of bias. The publication bias was tested by funnel plot and Egger’s test. Eighteen CKD incidence studies (n = 398,663) and six CKD progression studies (n = 13,575) were included. An inverse relationship was observed between UA levels and protection from CKD incidence and progression. Lower UA levels were protective for the risk of CKD incidence (RR 0.65 [95% CI 0.56–0.75]) and progression (RR 0.55 [95% CI 0.44–0.68]). UA seems to be implicated both in the genesis of CKD and its evolution.


Rationale
3 Describe the rationale for the review in the context of existing knowledge.
Page 3 Objectives 4 Provide an explicit statement of the objective(s) or question(s) the review addresses.
Page 4

Eligibility criteria 5
Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.
Page 5 Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted.

Pages 4 and 5
Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.

Pages 4 and 5
Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
Pages 4 and 5

No. Item Location where item is reported
Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.
Page 5 Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

Page 6
Effect measures 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results.
Pages 6 and 7 Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item 5)).

No. Item Location where item is reported
13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.
Pages 6 and 7 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.
Pages 6 and 7 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.
Page 7   13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression).
Page 7 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.
-Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).
Page 7 Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.
Page 7

Study selection 16a
Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.
Page 8 and Figure 1 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.

Eligibility criteria 3
Specify the inclusion and exclusion criteria for the review.

No
Information sources 4 Specify the information sources (e.g. databases, registers) used to identify studies and the date when each was last searched.

Yes
Risk of bias 5 Specify the methods used to assess risk of bias in the included studies.

Yes
Synthesis of results 6 Specify the methods used to present and synthesize results.

Included studies 7
Give the total number of included studies and participants and summarise relevant characteristics of studies.

Yes
Synthesis of results 8 Present results for main outcomes, preferably indicating the number of included studies and participants for each. If meta-analysis was done, report the summary estimate and confidence/credible interval. If comparing groups, indicate the direction of the effect (i.e. which group is favoured).

Limitations of evidence 9
Provide a brief summary of the limitations of the evidence included in the review (e.g. study risk of bias, inconsistency and imprecision).

No
Interpretation 10 Provide a general interpretation of the results and important implications.

Funding 11
Specify the primary source of funding for the review.

No
Registration 12 Provide the register name and registration number.